Guidance for registered pharmacies preparing unlicensed medicines
Revised August 2018
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© General Pharmaceutical Council 2018 Contents
About this guidance ...... 4
The scope of this guidance ...... 6
Introduction ...... 8
Guidance for registered pharmacies preparing unlicensed medicines ...... 10 1.1 Risk assessment ...... 10 1.2 Regular audit ...... 11 1.3 Reactive review ...... 11 1.4 Recall procedures ...... 12 1.5 Accountability – staff ...... 12 1.6 Record keeping ...... 12 2.1 Trained and competent staff...... 14 2.2 Training records ...... 15 3.1 Measures to minimise contamination...... 15 3.2 Hygiene control records ...... 16 4.1 Ingredients ...... 16 4.2 Quality assurance ...... 16 4.3 Patient information ...... 17 5.1 Specialist equipment and facilities ...... 18 5.2 Maintenance logs ...... 18 Other sources of information ...... 19
About this guidance This guidance should be followed if The General Pharmaceutical an unlicensed medicine is prepared in Council is the regulator for a registered pharmacy. pharmacists, pharmacy
technicians and registered The preparation of an unlicensed medicine (for pharmacies in England, example unlicensed methadone, or menthol in aqueous cream) in a pharmacy is called Scotland and Wales. ‘extemporaneous preparation’.
The guidance should be read alongside the standards for registered pharmacies. These aim to create and maintain the right environment, both organisational and physical, for the safe and effective practice of pharmacy. By following this guidance, the pharmacy will: • demonstrate that it meets our standards, and • provide assurances that the health, safety and wellbeing of patients and the public are safeguarded Responsibility for making sure this guidance is followed lies with the pharmacy owner. If the registered pharmacy is owned by a ‘body corporate’, the directors have responsibility. Those responsible for the overall safe running of the pharmacy need to take into account the nature of the pharmacy and the range of services already provided and, most importantly, the needs of patients and members of the public.
4 Guidance for registered pharmacies preparing unlicensed medicines
As well as meeting our standards, the pharmacy In this document, when we use the term ‘you’, owner must make sure they keep to all legal this means the pharmacy owner. requirements, including medicines legislation, In some limited circumstances (for example and health and safety, data protection and following death or bankruptcy), a representative equalities legislation. can take the role of the pharmacy owner. In Pharmacy owners should make sure that all staff, these cases, the appointed representative will be including non-pharmacists, involved in preparing responsible for making sure these standards are unlicensed medicines are familiar with this met. guidance. Individual pharmacy professionals are key to ensuring the safe preparation and supply of unlicensed medicines. Pharmacists and pharmacy technicians involved in preparing unlicensed medicines have a responsibility to provide medicines safely to patients, maintain the quality of their practice, keep their knowledge and skills up to date, and work within their professional competence. We expect this guidance to be followed. However, we also recognise that there can be a number of ways to meet our standards and achieve the same outcomes for patients – that is, to provide safe treatment, care and services. If you do not follow this guidance, you should be able to show how your alternative ways of working safeguard patients, identify and manage any risks, and meet our standards.
5 Guidance for registered pharmacies preparing unlicensed medicines
The scope of this guidance
This guidance applies only to the • the preparation of methadone for supply in accordance with a prescription (either for 1 process of preparing an unlicensed immediate supply in accordance with the medicine by (or under the supervision prescription, or initially as stock4 to be supplied from the pharmacy, by or under of) a pharmacist in a registered the supervision of a pharmacist, against a pharmacy in Great Britain, under the prescription at a later time) exemptions and circumstances • the preparation of an unlicensed medicine based upon the pharmacist’s judgement5 described in the law2. • the preparation of an unlicensed medicine by, or under the supervision of, a pharmacist It applies whether this happens rarely, based on the specification of the patient occasionally or is part of the core business of the registered pharmacy. If the activity is not covered by the exemptions set out in the law, you will need a Manufacturer’s This guidance applies to all the following: Specials (MS) licence from the Medicines and • the one-off preparation of an unlicensed Healthcare products Regulatory Agency (MHRA). medicine in accordance with a prescription If the medicines are being prepared for animal for an individual patient use, the exemptions that allow this, and the parts • the preparation of a stock3 of unlicensed of the law that apply, are found in the Veterinary medicines, (in anticipation of a prescription), Medicines Regulations 2013. The body that which will later be supplied from the regulates animal medicines and issues pharmacy, by or under the supervision of a authorisations to manufacturers of special pharmacist, against a prescription for an veterinary medicinal products is the Veterinary individual patient Medicines Directorate (VMD).
1 This guidance does not apply to unlicensed medicines that 4Preparation for stock at a pharmacy is acceptable as long as it is registered pharmacies have not prepared themselves, but have subsequently supplied by retail from that pharmacy or another obtained from elsewhere such as (MS) licensed manufacturers, pharmacy which is part of the same legal entity importers or distributors 5An unlicensed medicine that is prepared with the intention of 2 Section 10 of the Medicines Act 1968 and Regulation 4 of the selling it over the counter (one that is not a prescription-only Human Medicines Regulations 2012 medicine) is often called a ‘Chemist’s Nostrum’ 3 Preparation for stock at a pharmacy is acceptable as long as it is subsequently supplied by retail from that pharmacy or another pharmacy which is part of the same legal entity
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Throughout this document we use the terms ‘preparing’ and ‘preparation’ which refer to the extemporaneous preparation of a medicine from ingredients or starting materials. These terms are not intended to include the process of simply diluting or dissolving a product in a vehicle designed for that purpose as part of its marketing authorisation – for example, adding a set amount of water to reconstitute an antibiotic powder.
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Introduction
The law6 sets out the restrictions on appropriately prescribed licensed medicines are effective and meet the clinical needs of patients. how human medicines are licensed, As a rule, the law requires that only authorised manufactured, advertised, (licensed) medicines should be made available administered, sold and supplied. and supplied (‘placed on the market’). There are exemptions in the law which allow unlicensed medicines to be prescribed and supplied to Most of the medicines supplied from registered individual patients. pharmacies are licensed medicines. Licensed medicines are those that have a valid Marketing In general, when a prescriber issues a Authorisation (MA) in the UK, and which are prescription they will prescribe a medicine that is covered by an approval process overseen by the licensed and indicated for the condition to be MHRA or the European Medicines Agency (EMA). treated. European and UK law sets out the circumstances under which prescribers can The manufacturers who make or import these prescribe an unlicensed medicine for supply to medicines in the UK are also regulated and their patient. You can find more information on licensed by the MHRA for compliance with EU the prescribing of an unlicensed medicine by Good Manufacturing Practice (GMP) standards reading the General Medical Council’s (GMC’s) and the strict conditions of their licence. You can Good practice in prescribing and managing find more information about the approval medicines and devices on their website. and inspection of manufacturers on the MHRA’s website. Under the law, unlicensed medicines (‘special products’) must be manufactured by the holders These arrangements mean that licensed of MS (‘specials’) licences who are regulated by manufacturers are making medicines to a the MHRA and who follow GMP standards and regulated standard that is consistent throughout the conditions of their licences. the industry. It also means that when medicines are used in line with their licence, they are: In general, the law also requires the medicine itself be licensed7. However, the law8 allows a • assured to a certain level of efficacy, quality pharmacist to prepare and supply medicines in a and safety, and registered pharmacy without the need for the • only available if they are effective product to be licensed. A pharmacist should Overall this means that the public, and patients, have acquired the necessary knowledge and skill can have a high degree of confidence that to do this during their initial education and training leading to registration.
6 Medicines Act 1968 and the Human Medicines Regulations 2012 8 Section 10 of the Medicines Act 1968 and Regulation 4 of the 7 Regulations 46 of the Human Medicines Regulations 2012 Human Medicines Regulations 2012
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A patient has every right to expect that when an If you choose to prepare unlicensed medicines in unlicensed medicine is prepared by, or under the your pharmacy under the exemptions in the law, supervision of, a pharmacist in a registered you should follow the guidance set out in this pharmacy, it is of an equivalent quality to any document. licensed medicine they will receive (such as those The owner is responsible for making sure that produced by a regulated and licensed there are systems in place to safeguard the manufacturer). As certain high-profile past cases9 health, safety and wellbeing of patients and the have shown, preparing an unlicensed medicine public who use their services. This guidance in a pharmacy is an activity that can pose a covers the areas we believe may present an significant risk to patients and have potentially increased risk when medicines are prepared in a serious consequences when risks and processes registered pharmacy. It will help the owner to are not managed properly. meet our standards for registered pharmacies. When a patient is supplied with an unlicensed medicine, it is important that the unlicensed medicine is safe and appropriate. Pharmacists making supplies must also consider their individual professional standards and their responsibilities to the patient. There is also a general legal duty that all medicines supplied to patients are of the nature and quality requested or prescribed. The law also allows a pharmacist in a registered pharmacy to prepare medicines for animal use in line with a prescription, prescribed under the cascade10, from a veterinary practitioner. The authorised specials manufacturers of veterinary medicines are inspected by the VMD for their compliance with the principles of GMP. If they manufacture human medicines they would also be regulated by the MHRA under a separate licence.
9 Peppermint water case 10 Veterinary Medicines Regulations 2013 9 Guidance for registered pharmacies preparing unlicensed medicines
Guidance for registered pharmacies preparing unlicensed medicines
The standards for registered requirements of principle 1. If your intention is that your pharmacy will prepare medicines, you pharmacies are grouped under five will need to be able to produce evidence for the principles, and this guidance is set arrangements you have in place to manage the risks identified. out under each of the five principles. The risk assessment should be reviewed Principle 1: The governance regularly (see section 1.2) and should also be arrangements safeguard the health, reviewed when circumstances change (see safety and wellbeing of patients and the section 1.3). public. The risk assessment should state what the risks are, and should include finding out whether The following areas relate to this principle in the equivalent relevant licensed products exist and standards for registered pharmacies. are available. 1.1 Risk assessment While this is not a full list of issues that need to A risk assessment is a careful and thorough look be taken into account, the assessment should, if at what, in your work, could cause harm to applicable, look at: patients and what you need to do to prevent this. • a formula from a recognised source, for Risk assessments should be specific to the example from an official Pharmacopoeia individual pharmacy, the staff working in it, and to each unlicensed medicine to be prepared. • a verification of the preparation method (eg the Pharmacopoeia method) You should consider the risks before deciding whether your pharmacy should prepare • a calculation verification unlicensed medicines in general, or whether you • the use of specialist equipment might consider other options for supplying particular medicines. • consideration of contamination
You should carry out a risk assessment if an • hygiene measures unlicensed medicine is prepared in your • product-specific risks pharmacy, and carry out the necessary checks to satisfy yourself that any arrangements you have in place to manage the risks involved meet the
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• assurances around ingredients and starting • the premises (including temperature, light materials, including the supplier’s and moisture controls; and where applicable authorisation status – for example in aseptic preparation – air quality and other environmental • the suitability of premises requirements) • relevant staff skills • the equipment and facilities • training and competence • the preparation process and quality control • the circumstances that would trigger a new • the hygiene issues that might have an risk assessment adverse impact on the product and 1.2 Regular audit therefore the patient (including avoiding cross-contamination and microbial You should have robust systems in place so that contamination) you can demonstrate that your pharmacy: • staff training and skills • continues to be a safe place in which to prepare unlicensed medicines for patients, • the records (including the method of and preparation, traceability of ingredients used, labelling applied and how the records • can produce medicines which are safe, themselves are kept) effective and of a suitable quality You should learn from any incidents, complaints You should carry out a regular audit, at an or other forms of relevant information and use interval that you can show to be appropriate, on the learning to make appropriate changes. the process of preparing unlicensed medicines. The audit should form part of the evidence which 1.3 Reactive review provides assurance and shows that the A review should take place when any of the pharmacy continues to be safe and appropriate following happens: to carry out this activity. • changes in key staff (those who have While this is not a full list of issues that need to specialist training, knowledge and be taken into account, the audit should, if experience and are involved in preparing applicable, look at: medicines)
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• the introduction of new staff 1.5 Accountability – staff • a change in the equipment It should be clear which pharmacist is • a change in the form, or source, of accountable and responsible for the preparation ingredients of an unlicensed medicine. • any incidents It should also be clear which pharmacy technician and other staff are involved in • the environment or facilities available are no preparing an unlicensed medicine. longer fit for the task • concerns or feedback received 1.6 Record keeping • a review of near misses and error logs You should keep detailed records of the indicates concerns about this activity preparation of the unlicensed medicine to safeguard patients. This is so that if there is a This reactive review, which should be recall, or an incident affecting a patient’s safety, documented, should say when a new risk the method of preparation can be clearly assessment is needed. It can form part of that reconstructed. new risk assessment, when one needs to be carried out. You should keep records for as long as you consider, and can show, to be appropriate, 1.4 Recall procedures taking into account any consumer protection laws which apply. If the medicine being prepared It is important that if there is a problem with an is for animal use there are specific requirements unlicensed medicine that has been prepared in in the law for record keeping that also apply. Ask your pharmacy, you have the systems in place to the pharmacy’s professional indemnity insurance contact members of the public and recall provider for advice about how long you should unlicensed medicines that have been made in keep records for. your pharmacy. These procedures should say who is responsible for taking action, and what action to take. They should also include details of the other bodies or authorities that need to be told about the medicines’ recall. Under the standards you must have arrangements in place that allow all staff to raise concerns when they suspect that medicines are not fit for purpose.
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The records should include information on the following:
The process The ingredients (For each ingredient or starting material • Description of the key preparation used) steps used • Calculations: working shown and • The source: manufacturer, brand and double checked (detailed) the wholesaler or distributor 11 • The name of the person who prepared • Certificate of conformity (if applicable) the worksheet • Certificate of analysis12 (if applicable) • The date that the worksheet was • Batch number prepared • Expiry date (if available) • The name of the supervising • Quantity used and details of the person pharmacist (and the name of the measuring, and person double- pharmacist signing off the final product checking, quantities as ready to be supplied to the patient, if different) • TSE guidance13 should be followed (if applicable, that is, where an ingredient • The name of the pharmacy technician or product contact material is of animal involved (if applicable) origin) • Description of the container and The formula closure used (for example whether they were glass or plastic) • The complete formula • The source of the formula: Pharmacopoeia formula or other source • Validation of the formula
11 Certificate of conformity provides confirmation that the product 13 The TSE guidance is the European Commission’s ‘Notes for supplied complies with a specified set of requirements or guidance on minimising the risk of transmitting animal specifications, but does not contain any test results. spongiform encephalopathy agents via medicinal products’ and 12 Certificate of analysis provides a summary of testing results on future updates See the Other sources of samples of products or materials together with the evaluation for information section at the end of this document for more compliance to a stated specification information 13 Guidance for registered pharmacies preparing unlicensed medicines
Principle 2: Staff are empowered and The product competent to safeguard the health, • Date prepared safety and wellbeing of patients and the public. • A reference number or identification (batch number) The following areas relate to this principle in the standards for registered pharmacies. • Expiry date (give reasons or validation in support) 2.1 Trained and competent staff • Date supplied to the patient or Staff should complete recognised training customer courses before they can be involved in this activity. However, staff may also be involved in The patient or customer this activity if they are still doing such a training course, but their work in this area must be • The patient or customer’s name closely supervised until their training is complete. • The patient or customer’s address To prepare an unlicensed medicine from ingredients, staff need expertise and skill over • The patient or customer’s contact and above that needed to dispense a licensed details (for example, phone number, medicine. Many pharmacists and pharmacy email address) technicians should have acquired this knowledge • A sample of the label that has been put and skill during their initial education and on the medicine training leading to registration. If they do not • The name of the person who produced have the necessary knowledge, skills or the label competence to safely carry out the task, you should consider how you ensure that they obtain Also, if supplied against a prescription (or if they have previously been trained in this • The patient’s doctor (name, address area, refresh) the necessary specialist skills. and phone number) It is important that training is regularly repeated • The patient’s age (if it is on the to make sure that all staff remain up to date and prescription) competent. This is particularly important when the activity is only carried out from time to time. • Other prescription details (date and type) Staff working with potentially hazardous substances (such as cytotoxic products), or in areas that require more stringent precautions Incidents (such as aseptic preparation), should have done specific, recognised and relevant training. • Suspected adverse reactions reported • Complaints and concerns
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2.2 Training records Principle 3: The environment and You should document and keep evidence of the condition of the premises from which training done for as long as you consider, and pharmacy services are provided, and any can show, to be appropriate. These records associated premises, safeguard the should be made available to the relevant health, safety and wellbeing of patients authorities if they ask for them. and the public. You should ask the pharmacy’s professional You should assess the risks and consider indemnity insurance provider for advice on how whether your pharmacy premises are suited to, long you should keep records for. and capable of, providing this service. You should get specialist advice when you are considering preparing sterile (aseptic) or hazardous medicines (for example cytotoxics, hormones or immunosuppressants). There are highly specialised requirements for the safe preparation of aseptic medicines, and there are potentially significant adverse consequences to patients if there is an error with, or contamination of, these medicines. You should get specialist advice from regional NHS Quality Assurance staff (some of which also operate on a consultancy basis and can provide services across Great Britain and to non-NHS organisations too). See the Other sources of information section at the end of this document for more information on this subject. The following areas relate to this principle in the standards for registered pharmacies.
3.1 Measures to minimise contamination There should be enough space, and segregation where required, to provide this service safely, and the environment of the premises should be suitable for the preparation of medicines. Specific steps should be taken to make sure that the risk of cross-contamination and microbial
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contamination is eliminated or minimised within Principle 4: The way in which pharmacy the pharmacy. services, including the management of These factors should be considered as part of medicines and medical devices, are the initial risk assessment. delivered safeguards the health, safety
See the Other sources of information section at and wellbeing of patients and the public. the end of this document for links to information The following areas relate to this principle in the provided by governmental infection control standards for registered pharmacies. agencies. 4.1 Ingredients 3.2 Hygiene control records The ingredients and starting materials used in You should make records of the steps taken to the preparation of the unlicensed medicine will make sure that the environment, conditions and affect the quality of the final product. Therefore equipment are clean enough for the preparation you should make sure that any ingredients or of medicines. These will form part of the starting materials your staff use are obtained evidence that the pharmacy is suitable for the from a reputable source: for example, a licensed preparation of unlicensed medicines. manufacturer or distributor. You should keep the records for as long as you 4.2 Quality assurance consider, and can show, to be appropriate. You should ask the pharmacy’s professional Quality assurance, in this context, is the indemnity insurance provider for advice on how procedures, processes and arrangements in long you should keep records for. place that make sure a finished medicine is of the quality needed for its intended use. To have a robust system of quality assurance that provides the necessary safeguards, you need to have a range of systems in place, such as those described in this guidance. These include: • using worksheets and official formulas • confirmation of quantities and identities of ingredients • staff whose training is suitable and up to date, and • appropriately maintained equipment You should have procedures in place which include a specific method, process, or system that is used consistently to assure yourself that
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the unlicensed medicine produced is of suitable If the medicine is prepared in line with a British quality to be supplied to the patient. Pharmacopoeia (BP) formula or a general monograph in the BP for the dosage form, there When more than a single one-off preparation is are particular labelling requirements for made, this quality assurance should be robust unlicensed medicines. enough to safeguard all the patients who may be supplied from a single batch of medicines. There are also specific labelling requirements when the prepared medicine is for animal use, 4.3 Patient information which has been prescribed by a veterinary At the outset, you should make sure that there is practitioner under the cascade. a system in place so that the Responsible Pharmacist (or other staff competent to be delegated this task) tells the patient that the pharmacy will be preparing an unlicensed medicine. They should explain to the patient what this means (including what this means in relation to the amount of information and evidence available about the medicine). When a pharmacy supplies an unlicensed medicine there is no legal requirement to give a package leaflet, or similar detailed written information. Therefore the patient will rely on the information that your pharmacy staff give them. You should give appropriate advice and information (in writing if possible). This applies equally when there is limited, or no, direct contact with the patient when the medicine is supplied. You should make sure that the pharmacy staff give the patient any important information they might need so that they can use the medicine safely. The information should include advice on the use of any dosing device that needs explanation to deliver the correct dose. You should also make sure that pharmacy staff consider what extra information they should give the patient about the medicine: for example, the expiry date or any special storage instructions.
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Principle 5: The equipment and facilities 5.2 Maintenance logs used in the provision of pharmacy You should keep maintenance logs, including services safeguard the health, safety and validation and calibration records, for each type wellbeing of patients and the public. of specialist equipment for as long as you The following areas relate to this principle in the consider, and can show, to be appropriate. These standards for registered pharmacies. logs will form part of the evidence that the pharmacy is suitable for the preparation of 5.1 Specialist equipment and facilities medicines. You should make sure that the pharmacy has You should ask the pharmacy’s professional equipment and facilities which are specially indemnity insurance provider for advice on how designed for the intended purpose that staff will long you should keep records for. use them for. They should be of sufficiently high specification, and accuracy where applicable, to produce a high-quality, safe product. Examples of specialist equipment include, but are not limited to, the following: • accurate measuring devices for weight (measuring scales) • accurate measuring devices for volume (for example, cylinders) • production and mixing equipment • cleaning equipment (including suitable detergent) • contamination-minimising clothing (for example, masks, gloves, aprons, coats, hats) • sterilising equipment (including suitable chemical agents, autoclaves and filtration equipment) • fume cupboards, isolators and laminar flow cabinets
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Other sources of information
• Rules and Guidance for Pharmaceutical • PIC/S Guide to Good Practices for the Manufacturers and Distributors 2017 ‘The Preparation of Medicinal Products in Orange Guide’ (or any subsequent revision). Healthcare Establishments PE 010-4 2014 You can find more information on the • Resolution CM/Res(2016)1. The European MHRA’s website. Directorate for the Quality of Medicines and • European Commission’s ‘Notes for guidance Healthcare has passed a resolution on on minimising the risk of transmitting animal quality and safety assurance requirements spongiform encephalopathy agents via human for medicinal products prepared in and veterinary medicinal products pharmacies for the special needs of patients. • Veterinary medicines guidance for prescribing vets on the use of the cascade contains If you have questions or comments information on the extemporaneous about the content of this guidance, preparation of medicines. please contact our Policy and • The following agencies are a source of Standards Team: information on infection control: Policy and Standards Team – Health Protection Scotland General Pharmaceutical Council – Public Health England 25 Canada Square – Health Protection Agency (for Wales) London Other references that may be useful and of E14 5LQ interest include: 0203 713 8000 • Handbook of Extemporaneous Preparation, Ed. Jackson and Lowey on behalf of the NHS [email protected] Pharmaceutical Quality Assurance Committee, Pharmaceutical Press, 2010 We have also produced guidance on • Quality Assurance of Aseptic Preparation other topics that you may find useful: Services: Standards Handbook Edition 5, Ed. www.pharmacyregulation.org/ A.M. Beaney on behalf of the NHS standards/guidance Pharmaceutical Quality Assurance Committee, Pharmaceutical Press, 2016.
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